Cardiac function and the effect of heart failure treatment in patients with genotype-positive dilated cardiomyopathy

Background Dilated and non-dilated left ventricular cardiomyopathy (DCM/NDLVC) are commonly caused by pathogenic genetic variants. Heart failure (HF) treatment recommendations for genotype-positive patients with early disease are lacking. Purpose We aimed to assess HF outcome in HF treated and HF untreated DCM/NDLVC genotype-positive patients in early disease stages. Methods Genotype-positive DCM/NDLVC patients were enrolled in an observational follow-up study. We recorded the use of HF medication and analyzed echocardiographic examinations at baseline and last follow-up. Patients were stratified according to left ventricular (LV) ejection fraction (EF) as preserved (LVEF ≥50%), mildly reduced (LVEF 40-49%), and reduced (<40%). HF outcome was defined as decline of LVEF <40% in patients with preserved/mildly reduced LVEF. In patients with mildly reduced LVEF, all available echocardiographic examinations were analyzed by mixed model regression analyses stratified by HF treated and HF untreated. Genotype-specific analyses were performed for high-risk genotypes and low-risk genotypes. Results 712 DCM/NDLVC patients were followed for median 3.1 (1.3-5.6) years (mean age 40 years, 52% females, 20% probands). In 407 patients with preserved/mildly reduced LVEF, 24 (6%) patients declined to LVEF <40% during 3.2 (1.4-5.4) years of follow-up. Patients with high-risk genotypes more frequently progressed to LVEF <40% (n=16 (67%) vs. n=7 (33%); log-rank test P=0.04). In 130 patients with mildly reduced LVEF, who underwent a total of 449 echocardiographic examinations, HF treatment was associated with a higher absolute LVEF of 1.8% (95% confidence interval [CI], 0.7 to 2.9; P=0.01). Subgroup analyses showed a 1.6% higher LVEF (95% CI, 0.4 to 2.8; P=0.01) in HF treated compared to HF untreated examinations in patients with low-risk genotypes. In patients with high-risk genotypes, HF treatment was associated with a 2.4 % higher LVEF (95% CI, 0.3 to 4.4; P=0.02) compared to HF untreated examinations. The 82 patients with reduced LVEF at baseline echocardiography had a considerable effect of HF treatment with a LVEF increase of 16.8% (95% CI, 14.4 to 9.3; P<0.01). Subgroup analyses showed a LVEF increase of 18.0% (95% CI, 15.4 to 20.7; P<0.01) during 2.1 (0.8-5.5) years of follow-up in low-risk genotypes, and a LVEF increase of 12.8% (95% CI, 7.1 to 18.5; P<0.01) during 3.2 (1.2-8.7) years of follow-up in high-risk genotypes. Conclusions Early initiation of HF treatment in genotype-positive DCM/NDLVC patients with mildly reduced LVEF was associated with an increase in absolute LVEF of 1.8%. HF treatment improved LVEF both in patients with low-risk genotypes and high-risk genotypes. These results may help when planning larger trials for guideline-directed HF treatment in DCM/NDLVC patients.Survival free from LVEF <40%.LVEF progression: Patients with reduced LVEF.